A 7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl group is a suitable 7-position substituent for a quinolonecarboxylic acid antibacterial agent (corresponds to 10-position in case of pyridobenzoxazinecarboxylic acid derivative), and a quinolone compound having this substituent is a suitable antibacterial agent exhibiting excellent antibacterial activity, suitable pharmacokinetics, and high safety (Patent Document 1). The 7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl group has a chiral amino-substituted 7-position, which by itself generates a pair of optical isomers of a quinolone compound. It has been previously revealed that one of the isomers exhibits more potent antibacterial activity and further expresses other physiological activities compared to the other isomer (Patent Document 1).
A quinolone compound having the above substituent is readily produced from a 7-amino-7-methyl-5-azaspiro[2.4]heptane compound, and in an easier manner, by use of one optically active form of said compound. One exemplary method for producing the compound is represented by the following scheme (Patent Document 1):
(wherein Boc represents a tert-butoxycarbonyl group and R12 represents a C1 to C6 alkyl group).
Specifically, the previous method for producing the aforementioned compound (A) is characterized by the following steps: producing an amino-cyano compound from an acetoacetate ester compound through Strecker reaction at ketone moiety thereof; transforming a cyano group of the amino-cyano compound to an aminomethyl group; and then subjecting the aminomethyl group to intramolecular cyclization with an ester moiety (carboxyl unit) to form a pyrrolidone derivative.
Patent Document 1: Japanese Patent Application No. 2005